Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Madonna R
PROVIDER: S-EPMC6351940 | biostudies-other | 2019 Jan
REPOSITORIES: biostudies-other
Publications
Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease.
Madonna Rosalinda R Balistreri Carmela Rita CR De Rosa Salvatore S Muscoli Saverio S Selvaggio Stefano S Selvaggio Giancarlo G Ferdinandy Péter P De Caterina Raffaele R
Journal of clinical medicine 20190116 1
Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different ...[more]
Similar Datasets
Project description:OBJECTIVE:To examine secular trends and geographical variations in sex differences in mortality from coronary heart disease and investigate how these relate to distributions in risk factors. DESIGN:National and international data were used to examine secular trends and geographical variations in sex differences in mortality from coronary heart disease and risk factors. SETTING:England and Wales, 1921-98; Australia, France, Japan, Sweden, and the United States, 1947-97; 50 countries, 1992-6. DATA SOURCES:Office for National Statistics, World Health Organization, and Food and Agriculture Organization of the United Nations. RESULTS:The 20th century epidemic of coronary heart disease affected only men in most industrialised countries and had a very rapid onset in England and Wales, which has been examined in detail. If this male only epidemic had not occurred there would have been 1.2 million fewer deaths from coronary heart disease in men in England and Wales over the past 50 years. Secular trends in mean per capita fat consumption show a similar pattern to secular trends in coronary heart disease mortality in men. Fat consumption is positively correlated with coronary heart disease mortality in men (r(s)=0.79; 95% confidence interval 0.70 to 0.86) and inversely associated with coronary heart disease mortality in women (-0.30; -0.49 to -0.08) over this time. Although sex ratios for mortality from coronary heart disease show a clear period effect, those for lung cancer show a cohort effect. Sex ratios for stroke mortality were constant and close to unity for the entire period. Geographical variations in the sex ratio for coronary heart disease were associated with mean per capita fat consumption (0.64; 0.44 to 0.78) but were not associated with the sex ratio for smoking. CONCLUSION:Sex differences are largely the result of environmental factors and hence not inevitable. Understanding the factors that determine sex differences has important implications for public health, particularly for countries and parts of countries where the death rates for coronary heart disease are currently increasing.
| S-EPMC48158 | biostudies-literature
Project description:BackgroundType 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS.MethodsWe tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms.ResultsIn the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10- 59). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10- 4) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10- 3).ConclusionsPolygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.
| S-EPMC6993460 | biostudies-literature
Project description:Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions.
| S-EPMC7010648 | biostudies-literature
Project description:Studies exploring the association between insulin resistance (IR) and cardiovascular disease in blacks have not been conclusive, especially for coronary heart disease (CHD). The McAuley index and homeostasis model assessment of IR (HOMA-IR) perform differently in predicting cardiovascular disease. We investigated this association in the Jackson Heart Study, a large longitudinal cohort of blacks. IR was estimated for 3565 participants without diabetes mellitus and cardiovascular disease at baseline using the McAuley index and HOMA-IR, and their associations with incident CHD and stroke (composite outcome) were compared. A lower McAuley index and higher HOMA-IR are indicative of IR. Cox regression analysis was used to estimate adjusted hazard ratios for incident CHD and/or stroke. There were 158 events (89 CHD-only, 58 stroke-only, and 11 CHD/stroke) over a median follow-up of 8.4 years. After adjustment for demographic factors, the risk of the composite outcome decreased with each SD increase in the McAuley index (hazard ratio 0.80; 95% CI: 0.67-0.96), with no attenuation after further accounting for CHD and stroke risk factors. When considered individually, McAuley index and HOMA-IR were associated with CHD (hazard ratio 0.71, 95% CI: 0.55-0.92 and hazard ratio 1.33, 95% CI: 1.03-1.72, respectively), but not stroke risk. The logHOMA-IR and CHD association was present in men, but not in women (Pinteraction=0.01). Both HOMA-IR and the McAuley index demonstrate strong associations with CHD but not stroke risk in blacks. The logHOMA-IR and CHD association was present in men, but not in women.
| S-EPMC5523745 | biostudies-literature
Project description:Our understanding of sex differences in subclinical atherosclerosis and plaque composition and characteristics have greatly improved with the use of coronary computed tomography (CCTA) over the past years. CCTA has emerged as an important frontline diagnostic test for women, especially as we continue to understand the impact of non-obstructive atherosclerosis as well as diffuse, high risk plaque as precursors of acute cardiac events in women. Based on its ability to identify complex plaque morphology such as low attenuation plaque, high risk non calcified plaque, positive remodeling, fibrous cap, CCTA can be used to assess plaque characteristics. CCTA can avoid false positive of other imaging studies, if included earlier in assessment of ischemic symptoms. In the contemporary clinical setting, CCTA will prove useful in further understanding and managing cardiovascular disease in women and those without traditional obstructive coronary disease.
| S-EPMC9358989 | biostudies-literature
Project description:BackgroundWomen with type 2 diabetes (T2D) have a 50% excess risk of coronary heart disease (CHD) than men with T2D. We compared circulating metabolites and their associations with CHD in men and women across glycemic status.MethodsWe used metabolomic data (lipoproteins, fatty acids, amino acids, glycolysis, ketones, inflammation, and fluid balance) for 87,326 CHD-free UK Biobank participants. We used linear regressions to examine the association of sex and metabolites (log) in newly diagnosed T2D (diagnosis<2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia, accounting for age, race, Deprivation Index, income, smoking, alcohol drinking, obesity, physical activity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox models to evaluate the association of metabolites and CHD risk by sex, adjusting the same covariates and menopausal status (women). All analyses were FDR-adjusted.FindingsWe included 1250 individuals with new T2D, 12,706 with prediabetes, and 83,315 with euglycemia. In adjusted linear regressions, women showed a progressive increase in atherogenic lipid and lipoprotein markers and inflammatory marker, glycoprotein acetyls, compared to men as their glycemic status advanced. However, women had lower levels of albumin during this transition. Menopausal status did not alter these sex differences. In a 10-year follow-up, an SD higher total TG, TG in VLDL, LDL, and HDL, saturated fatty acids (SFA) were positively associated with a higher risk of CHD in women with T2D but not in men (p-interactions 0.03-0.15).InterpretationWith advancing glycemic status, women exhibited higher levels of atherogenic lipids and lipoproteins, as well as inflammatory markers, but lower circulating albumin. Women with T2D appear to be at a higher risk of CHD associated with TG, VLDL-TG, LDL-TG, and HDL-TG, and SFA than men with T2D.
| S-EPMC11302618 | biostudies-literature
Project description:Background and purposeEpidemiological studies have documented that plasma d-dimer, a fibrin degradation product, is a risk marker for coronary heart disease, but there is limited prospective evidence for stroke. Given that thrombosis is a key mechanism for many strokes, we studied whether d-dimer is a risk marker for ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsWe measured d-dimer in 11 415 ARIC participants free of stroke and coronary heart disease in 1992 to 1995. We followed them for stroke, stroke subtype, and coronary heart disease events through 2012.ResultsOver a median of 18 years of follow-up, 719 participants had incident strokes (628 ischemic and 91 hemorrhagic). d-dimer was associated positively with risk of total, ischemic, and cardioembolic strokes, with risk elevated primarily for the highest quintile of d-dimer. After adjustment for other cardiovascular risk factors, the hazard ratio for the highest versus lowest quintile of d-dimer was 1.30 (95% confidence interval, 1.02-1.67) for total stroke, 1.33 (95% confidence interval, 1.02-1.73) for ischemic stroke, and 1.79 (95% confidence interval, 1.08-2.95) for cardioembolic stroke. There was no association with hemorrhagic, lacunar, or nonlacunar stroke categories. d-dimer was positively but weakly associated with coronary heart disease incidence.ConclusionsA higher basal plasma d-dimer concentration in the general population is a risk marker for ischemic stroke, especially cardioembolic stroke.
| S-EPMC4696899 | biostudies-literature
Project description:Chromogranin A (CgA), B (CgB), and C (CgC), the family members of the granin glycoproteins, are associated with diabetes. These proteins are abundantly expressed in neurons, endocrine, and neuroendocrine cells. They are also present in other areas of the body. Patients with diabetic retinopathy have higher levels of CgA, CgB, and CgC in the vitreous humor. In addition, type 1 diabetic patients have high CgA and low CgB levels in the circulating blood. Plasma CgA levels are increased in patients with hypertension, coronary heart disease, and heart failure. CgA is the precursor to several functional peptides, including catestatin, vasostatin-1, vasostatin-2, pancreastatin, chromofungin, and many others. Catestatin, vasostain-1, and vasostatin-2 suppress the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular endothelial cells. Catestatin and vasostatin-1 suppress oxidized low-density lipoprotein-induced foam cell formation in human macrophages. Catestatin and vasostatin-2, but not vasostatin-1, suppress the proliferation and these three peptides suppress the migration in human vascular smooth muscles. Chronic infusion of catestatin, vasostatin-1, or vasostatin-2 suppresses the development of atherosclerosis of the aorta in apolipoprotein E-deficient mice. Catestatin, vasostatin-1, vasostatin-2, and chromofungin protect ischemia/reperfusion-induced myocardial dysfunction in rats. Since pancreastatin inhibits insulin secretion from pancreatic β-cells, and regulates glucose metabolism in liver and adipose tissues, pancreastatin inhibitor peptide-8 (PSTi8) improves insulin resistance and glucose homeostasis. Catestatin stimulates therapeutic angiogenesis in the mouse hind limb ischemia model. Gene therapy with secretoneurin, a CgC-derived peptide, stimulates postischemic neovascularization in apolipoprotein E-deficient mice and streptozotocin-induced diabetic mice, and improves diabetic neuropathy in db/db mice. Therefore, CgA is a biomarker for atherosclerosis, diabetes, hypertension, and coronary heart disease. CgA- and CgC--derived polypeptides provide the therapeutic target for atherosclerosis and ischemia-induced tissue damages. PSTi8 is useful in the treatment of diabetes.
| S-EPMC8201018 | biostudies-literature
Project description:BackgroundPolymorphisms within natriuretic peptide (NP) genes have been associated with clinical outcomes for cardiovascular disease (CVD), but no previous study has compared the effect of these polymorphisms between men and women. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in key genes of the NP system and coronary angiographic outcomes, with the focus on the sexual dimorphism in the effects of these SNPs.MethodsPatients undergoing clinically indicated coronary angiography (n = 513, 328 men and 185 women) were consented and genotyped for NPPA rs5065, NPPB rs198389 and NPR2 rs10758325. Patients were stratified into having normal coronaries, non-obstructive coronary artery disease (CAD) or obstructive CAD, based on the highest stenosis in any epicardial artery. Average luminal narrowing across all four arteries was derived to represent the overall atherosclerotic burden.ResultsThe frequency of NPPB rs198389 AA genotype was significantly higher in women with obstructive CAD (P = 0.014). The same association was not observed in males. With respect to atherosclerotic burden, an association was found between the AA genotype and average luminal narrowing in women (P = 0.005), but not in men.ConclusionsThe current study identified an association between an SNP of the NPPB gene and coronary atherosclerotic burden through angiographic evidence in women but not in men. These results suggest that B-type natriuretic peptide (BNP) may have more important involvement in the development of CAD in women compared to men, and as such, genotyping of the NPPB gene may serve as a potential biomarker to identify women with high risk for CAD.
| S-EPMC5340518 | biostudies-literature
Project description:Background Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis-related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque-count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty-one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history (P=0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2-2.1; P<0.01) and 1.4 (95% CI, 1.0-1.9; P=0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0-2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4-1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1-3.9), which was statistically significant from the interaction test, P=0.04. Conclusions Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti-hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.
| S-EPMC9238545 | biostudies-literature